Background: Elevated gestational circulating testosterone has been associated with pathological pregnancies, such as preeclampsia which causes fetal growth restriction and increase the risk of development of hypertension and metabolic disturbances in adult life. Dipeptidyl peptidase-4 (DPP-4) is important in the regulation of postprandial glucose and vascular tone and also plays a role in inflammation. However, the role of DPP-4 in pathological pregnancies caused by elevated gestational testosterone has not been determined. 
Aim: The study was designed to investigate the effect of elevated maternal testosterone on glucose deregulation, endothelial dysfunction markers and fetal outcome. The study also examined the possible role of DPP-4 activity. 
Methods: Pregnant Wistar rats were treated (s.c.) with either olive oil or testosterone (0.5 mg/kg) between gestational days 14 and 19. Glucose tolerance and insulin resistance was estimated by oral glucose tolerance test (OGTT) and homeostatic model of assessment (HOMA-IR) respectively. Malondialdehyde (MDA) was estimated by colorimetry, plasma insulin, testosterone, vascular cell adhesion molecule-1 (VCAM-1) were determined by enzyme-linked immunosorbent assay while DDP-4 activity was determined by fluorescence assay. The fetal weight, placental weight, number of fetus as well as fetal resorption were evaluated as fetal outcome. 
Result: The results show that elevated maternal testosterone led to increase in fasting blood glucose, 1hr-postload glucose level, insulin resistance, circulating insulin, MDA, VCAM-1, and DPP-4 activity as well as number of fetal resorptions. On the other hand, elevated maternal testosterone led to decreases in fetal weight, placental weight and number of fetus. However, elevated maternal testosterone did not affect glucose tolerance. 
Discussion: The results from this study demonstrate that elevation of maternal testosterone would cause glucose deregulation and endothelial dysfunction that are accompanied with increased activity of dipeptidyl peptidase–4. The data from this finding suggests that increased activity of DPP-4 may play a pathophysiological role in the development of cardiometabolic disturbances as well as poor fetal outcome.

Elevated gestational testosterone causes insulin resistance and increases dipeptidyl peptidase–4 activity in rats